DNA cleavage and antitumoral activity of zinc(II) and iron(III) complexes with a new phenol-based ligand containing uncoordinated thioether moieties.

In this study, a novel ligand: 2-((bis(2-(phenylthio)ethyl)amino)methyl)-6-((bis(pyridin-2-ylmethyl)amino)methyl)-4-methylphenol (HL) was prepared and subsequently used to synthesize the complexes [Zn(L)(OAc)]ClO4 (1) and [Fe2(L)(μ-OAc)(μ-O)](ClO4)2 (2). The metal complexes were comprehensively characterized using different techniques such as IR, Mass Spectrometry, UV-Vis, elemental analysis and X-ray analysis. The crystal structures show that compound 1 is a mononuclear pentacoordinate zinc(II) complex, while compound 2 is a dinuclear hexacoordinate iron(III) compound, with the metal centers connected by μ-oxo and μ-acetato bridges. In both cases, the phenol-based ligand features thioether substituents as pendant arms. We have evaluated the binding of the new complexes to DNA and also their capacity to cleave it. Both complexes have excellent antitumor activity against an astrocytic tumor derived from a primary human GBM1 cell line. SYNOPSIS: The paper reports synthesis and characterization of two new complexes [Zn(L)(OAc)]ClO4 (1) and [Fe2(L)(μ-OAc)(μ-O)](ClO4)2 (2). Complex 1 exhibits better activity than 2 at lower concentrations and with a faster rate of action, showing a preference for the minor groove. The cytotoxicity studies demonstrated a reduction in cell viability when exposed to the complexes, with GBM and C6 cells.